scholarly journals New Natural Intergenotypic (2/5) Recombinant of Hepatitis C Virus

2007 ◽  
Vol 81 (8) ◽  
pp. 4357-4362 ◽  
Author(s):  
Florence Legrand-Abravanel ◽  
Julie Claudinon ◽  
Florence Nicot ◽  
Martine Dubois ◽  
Sabine Chapuy-Regaud ◽  
...  

ABSTRACT A 9.2-kb sequence from a hepatitis C virus (HCV) strain found in southwest France was compared to sequences from reference strains in HCV sequence databases. We found a recombinant virus with genotype 2 at the 5′ end and genotype 5 at the 3′ end. The crossover point was located between genes NS2 and NS3. Recombination between HCV genotypes must now be considered in studies on HCV epidemiology and evolution and in predictions of the virus response to antiviral therapy. Knowing the location of the recombination point may also be useful for constructing infectious chimeric viruses.

2006 ◽  
Vol 59 (5-6) ◽  
pp. 230-234 ◽  
Author(s):  
Dragan Delic ◽  
Zorica Nesic ◽  
Jasmina Simonovic ◽  
Neda Svirtlih ◽  
Ljubisa Dokic ◽  
...  

Introduction. Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. Material and methods. For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested. Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype lb infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. Results. Patients infected by genotype lb had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p<0.05). Over 70% of patients infected by genotype lb had more than 2xl06 virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7x10.6 virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3xl06 copies/ml; p<0.05). Conclusion. Our results are in concordance with the results of other authors reporting that genotype lb is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype lb infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems. .


2006 ◽  
Vol 80 (15) ◽  
pp. 7569-7577 ◽  
Author(s):  
Suwanna Noppornpanth ◽  
Truong Xuan Lien ◽  
Yong Poovorawan ◽  
Saskia L. Smits ◽  
Albert D. M. E. Osterhaus ◽  
...  

ABSTRACT Hepatitis C viruses (HCVs) display a high level of sequence diversity and are currently classified into six genotypes and an increasing number of subtypes. Most likely, this heterogeneity is caused by genetic drift; evidence for recombination is scarce. To study the molecular heterogeneity of HCV in Vietnam, we analyzed 58 HCV RNA-positive sera from Vietnamese blood donors by sequence analysis of the CORE and NS5B regions. Phylogenetic analyses revealed the presence of genotype 1 (38%), genotype 2 (10.3%), and genotype 6 viruses (51.7%). All samples showed concordant results except for two (D3 and D54). Sample D54 was a mixed infection of genotype 2i and 6h viruses. Whole-genome analysis and bootscan analysis of sample D3, on the other hand, revealed a recombinant virus with genotype 2i and genotype 6p sequences at the 5′ and 3′ ends, respectively. The crossover point was located between nucleotide positions 3405 to 3464 (numbering according to prototype strain HCV-H, M67463) at the NS2/NS3 junction. The identification of this naturally occurring recombinant virus strengthens the concept that recombination may play a role in HCV epidemiology and evolution. Furthermore, the location of the recombination breakpoint may be relevant for constructing infectious chimeric viruses.


2019 ◽  
Vol 57 (7) ◽  
Author(s):  
Kai-Henrik Peiffer ◽  
Lisa Kuhnhenn ◽  
Evelyn Stelzl ◽  
Julia Dietz ◽  
Simone Susser ◽  
...  

ABSTRACT Besides seven major hepatitis C virus (HCV) genotypes (GT), a number of intergenotypic recombinant strains have been described. These so-called chimeras combine genetic characteristics of different HCV genotypes. However, correct genotype classification is important, as choice and duration of direct-acting antiviral (DAA) treatment is mainly based on the viral genotype. Therefore, misclassification of chimeras might lead to suboptimal treatment of patients infected with these strains. For example, 2k/1b chimeras are typically described as HCV genotype 2 strains by commercially available hybridization assays, but real-time PCR-based tests recognizing another HCV region might be more suitable for correct chimera detection. In this study, the analytic capacity of the hybridization-assay Versant HCV Genotype 2.0 (LiPA 2.0) and the real-time PCR-based-assays cobas HCV GT and Abbott RealTime HCV Genotype II were tested in a selected cohort of 230 patients infected with HCV genotype 1 (n = 53) and 2 (n = 177) and 48 patients infected with HCV 2/1 chimeric strains. While the Versant HCV Genotype 2.0 (LiPA 2.0) assay failed to identify chimeras in all of the patients (48/48, 100%), cobas HCV GT and Abbott HCV Genotype II assays identified chimeras correctly in 90% (43/48) and 65% (31/48) of the cases, respectively. In conclusion, while the hybridization-based Versant HCV Genotype 2.0 (LiPA 2.0) assay seems to be unsuitable for detection of HCV 2/1 chimeras, use of the real-time PCR-based assays cobas HCV GT and Abbott RealTime HCV Genotype II led to a higher rate of chimera detection.


2009 ◽  
Vol 62 (3-4) ◽  
pp. 129-132
Author(s):  
Velimir Kostic ◽  
Marina Djordjevic ◽  
Lidija Popovic ◽  
Emina Kostic ◽  
Jovana Djordjevic ◽  
...  

Introduction. HCV infection was common cause of morbidity and mortality in patients with hemophilia before 1986. We wanted to investigate the effect of treatment with combination therapy in HCV positive patients with hemophilia. Material and methods. The research included totally 13 persons afflicted with hemophilia and HCV infection out of 21 tested. The patients were submitted to laboratory and clinical tests as well as genotypization, whereby a different hepatitis C virus genetic adherence was observed. Parallel with this subcategory the other one was put into comparison, consisting of 12 patients afflicted with chronic C hepatitis, marked as non-hemophilics. The both subcategories were treated with combination antiviral therapy (peginterferon a-2a and ribavirin) during 48 weeks for genotype 1 and 4, in reference to 24 weeks for genotype 2 and 3. Within the treatment, clinical and laboratory side-effects were noticed, which did not require therapy interruption. A more frequent hemorrhage during the therapy was found within the hemophilics, rather than before initiliazing it. Results. After the statistical processing of the results (Students' t-test), statistically significant difference among these two subcategories was noticed as values for ALT (***p<0.0001) after 24 weeks of therapy, red blood cells (*p<0.05), haemoglobin and haematocrite (***p<0.0001) 24 weeks after therapy completing. By PCR examination of the patients, 6 months after the end of treatment, a sustained viral response (SVR) of the same percentage was registrated within both subcategories, which is even greater than what the other authors have described. Discussion. Main results were without important difference between two subgroups, except for higher number of spontanuous bleeding in group with hemophilia, which was somewhat expected. Most importantly, we didn't find any difference in SVR rates between groups. Conclusion. HCV positive patients with hemophilia could be successfully treated with combination therapy of peginterferon alfa-2a and ribavirin.


2004 ◽  
Vol 85 (7) ◽  
pp. 1853-1857 ◽  
Author(s):  
Olga Kalinina ◽  
Helene Norder ◽  
Lars O. Magnius

The full-length ORFs for the hepatitis C virus recombinant RF1_2k/1b (N687) and the non-recombinant 1b strain N589 were sequenced. A single recombination point was found and the sizes of the genes (C, E1, E2, p7, NS2, NS3, NS4 and NS5) were according to the parental subtypes. The PKR-eIF2α phosphorylation site homology domain sequence of the E2 protein was identical to those of genotype 2 strains, while the IFN-α-sensitivity-determining region of the NS5A protein was identical to those of interferon-resistant 1b strains. For the parental strains, two hairpin structures, HS1 and HS2, were predicted for the plus-strand up- and downstream of the crossover site, which were not present in the recombinant strain. HS2 shared similarity with the motif1 hairpin of turnip crinkle virus RNA that binds to the RNA-dependent RNA polymerase and facilitates 3′-terminal extension during recombination. This study suggests that RF1_2k/1b has emerged by homologous recombination during minus-strand synthesis via template switching because of constraints imposed by the HS1 hairpin of the 3′-parental genome.


2016 ◽  
Vol 60 (4) ◽  
pp. 2402-2416 ◽  
Author(s):  
Juan Ángel Patiño-Galindo ◽  
Karina Salvatierra ◽  
Fernando González-Candelas ◽  
F. Xavier López-Labrador

ABSTRACTThere is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype.


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